截短与修饰的β-淀粉样蛋白与阿尔茨海默病  

Truncated and Modified Aβ Species in Alzheimer’s Disease

作　　者：李高 李艳梅[2,3,4] Gao Li;Yan-Mei Li(Institute of Oceanography,Minjiang University,Fuzhou 350108,China;Department of Chemistry,Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology(Ministry of Education),Tsinghua University,Beijing 100084,China;Beijing Institute for Brain Disorders,Beijing 100069,China;Center for Synthetic and Systems Biology,Tsinghua University,Beijing 100084,China)

机构地区：[1]闽江学院海洋研究院,福州350108 [2]清华大学化学系生命有机磷化学及化学生物学教育部重点实验室,北京100084 [3]北京脑重大疾病研究院,北京100069 [4]清华大学合成与系统生物学研究中心,北京100084

出　　处：《化学进展》2020年第1期14-22,共9页Progress in Chemistry

基　　金：国家重点研发计划(No.2018YFA0507600);国家自然科学基金项目(No.81661148047);闽江学院人才引进项目(No.MJY19025)资助。

摘　　要：淀粉样蛋白(Aβ)的聚集和沉积被认为是导致阿尔茨海默病的重要因素,早前的研究多集中在全长无修饰的Aβ1-40和Aβ1-42上。近些年研究发现,在AD患者大脑内存在着多种截短与修饰的Aβ蛋白,它们对AD的疾病进程有不可忽视的贡献。例如,焦谷氨酸Aβ、磷酸化Aβ被认为是AD患者出现症状的标志;截短的Aβ4-40/42在患者脑内的含量与Aβ1-40/42接近且具有类似的聚集性质和毒性;患者脑内氧化压力升高导致的酪氨酸硝基化、二聚化和甲硫氨酸氧化形式的Aβ也具有不同的性质。本文对这些截短与修饰的Aβ蛋白的产生、结构、毒性以及和AD的关联进行了综述。Aggregation of β-amyloid(Aβ) has been considered as an important factor leading to Alzheimer’s disease(AD).Previous studies have focused on the full-length unmodified and Aβ1-42.In recent years,it was found that a variety of truncated and modified Aβ species co-exist in AD patients’ brain.These Aβ species contributed to the progression of AD and should not be overlooked.For example,the emergence of pyroglutamated Aβ and phosphorylated Aβ is considered as symptoms of AD.And the most abundant Aβ species in AD patients’ brain should be Aβ4-40/42,which has similar aggregation properties and toxicity with Aβ1-40/42·Due to the elevated oxidative stress in AD patients ’ brain,tyrosine nitration,dimerization and methionine oxidation were also identified in Aβ sequence,resulting in different properties.We review here the production,structure and toxicity of different Aβ species and summarize their possible roles in AD pathology.

关 键 词：Β-淀粉样蛋白 阿尔茨海默病 截短 磷酸化 焦谷氨酸化 

分 类 号：O621.3[理学—有机化学] R742[理学—化学]